What is the pathophysiology of pleurisy?

Pathophysiology of Pleurisy

Pleurisy develops when inflammatory processes disrupt the normal pleural space equilibrium, transforming the thin lubricating film between visceral and parietal pleura into an inflammatory exudate through immune activation, infection, or mechanical injury.

Normal Pleural Physiology

Understanding pleurisy requires first knowing the baseline state:

• The pleural space normally contains less than 1 mL of fluid total, forming a film approximately 10 μm thick between the visceral and parietal pleural surfaces 1.
• Normal pleural fluid volume is 0.3 mL/kg body weight, containing predominantly mesothelial cells, macrophages, and lymphocytes with protein concentrations similar to interstitial fluid 2, 3.
• Lymphatic vessels can clear several hundred milliliters of excess fluid per 24 hours before clinical effusion develops, maintaining this delicate equilibrium 2, 3.
• Normal pleural fluid has higher bicarbonate levels than serum, lower sodium levels, and similar glucose levels, with large molecular weight proteins like lactate dehydrogenase (LDH) present 1, 3.

Mechanisms of Pleural Inflammation

Infectious Pathway

Pneumonia is the most common trigger, with up to 57% of pneumonia patients developing pleural fluid 1:

• Bacterial invasion from adjacent lung parenchyma initiates the inflammatory cascade, with organisms penetrating the visceral pleura more easily than through the diaphragm or chest wall 4.
• The pleura responds with a standardized inflammatory sequence: initial exudation, cellular infiltration, fibrin deposition, and potential organization into fibrous adhesions 4.
• Anaerobic organisms are increasingly recognized, present in 12-76% of cases depending on the series, with anaerobes alone causing empyema in 14% of culture-positive cases 1.

Progressive Stages of Parapneumonic Effusion

The British Thoracic Society guidelines describe three distinct pathophysiologic stages 1:

1. Simple parapneumonic effusion: Clear fluid with pH >7.2, LDH <1000 IU/L, glucose >2.2 mmol/L, and negative cultures—represents early inflammatory response that typically resolves with antibiotics alone.

2. Complicated parapneumonic effusion: Cloudy/turbid fluid with pH <7.2, LDH >1000 IU/L, indicating advanced inflammation with bacterial metabolic activity overwhelming local buffering capacity—requires drainage.

3. Empyema: Frank pus accumulation representing complete breakdown of local immune control with massive bacterial proliferation and neutrophil death—requires aggressive drainage.

Non-Infectious Inflammatory Pathways

Asbestos exposure demonstrates chronic inflammatory mechanisms 1:

• Acute asbestos-related pleuritis can occur with or without effusion, sometimes presenting only as incidental radiographic findings or friction rub 1.
• The lesion develops from infolding of thickened visceral pleura with collapse of intervening lung parenchyma, creating conditions like rounded atelectasis (also called shrinking pleuritis or contracted pleurisy) 1.
• Chronic inflammation leads to fibrosis and adhesions between visceral and parietal pleura, with restrictive impairment and preserved diffusing capacity 1.

Key Pathophysiologic Alterations

When disease processes activate immune responses in adjacent lung or vascular tissue, critical parameters change 1:

• pH drops below 7.2 due to bacterial metabolism, increased CO2 production, and lactic acid accumulation from neutrophil glycolysis.
• LDH rises above 1000 IU/L reflecting cellular death and membrane breakdown.
• Glucose falls below 2.2 mmol/L as bacteria and inflammatory cells consume available substrate.
• Protein concentration increases as vascular permeability rises and large molecules leak into the pleural space.

Clinical Pitfalls

The flat serosal surfaces in constant motion against each other modify the typical inflammatory response 4:

• "Kissing lesions" can develop where infected visceral pleural lesions create mirror-image parietal lesions of identical size and shape, indicating attachment and splinting of pleural surfaces 4.
• Uncomplicated empyema can resolve to an almost undetectable scar in experimental models, while thick fibrotic pleural lesions suggest complicated courses with continuing infection 4.
• Primary empyema can develop without evidence of pneumonia, representing direct pleural space inoculation through trauma, procedures, or hematogenous spread 1.